1. Field of the Invention
The present invention relates to osmotic and diffusion controlled implantable delivery devices, and more particularly, to a delivery system with a membrane plug which controls the delivery rate of a beneficial agent from the delivery system.
2. Description of the Related Art
Controlled delivery of beneficial agents, such as drugs, in the medical and the veterinary fields has been accomplished by a variety of methods, including implantable delivery devices such as implantable osmotic delivery systems and implantable diffusion controlled delivery systems. Osmotic delivery systems are very reliable in delivering a beneficial agent over an extended period of time called an administration period. In general osmotic delivery systems operate by imbibing fluid from an outside environment and releasing corresponding amounts of a beneficial agent from the delivery system.
Osmotic delivery systems, commonly referred to as "osmotic pumps," generally include some type of capsule having walls which selectively pass water into the interior of the capsule containing a water attracting agent. The absorption of water by the water attracting agent within the capsule reservoir creates an osmotic pressure within the capsule which causes a beneficial agent within the capsule to be delivered. The water attracting agent may be the beneficial agent being delivered to the patient, however, in most cases, a separate agent is used specifically for its ability to draw water into the capsule.
When a separate osmotic agent is used, the osmotic agent may be separated from the beneficial agent within the capsule by a movable dividing ember or piston. The structure of the capsule is generally rigid such that as the osmotic agent takes in water and expands, the capsule does not expand. As the osmotic agent expands, the agent causes the movable dividing member or piston to move discharging the beneficial agent through an orifice or exit passage of the capsule. The beneficial agent is discharged through the exit passage at the same volumetric rate that water enters the osmotic agent through the semipermeable walls of the capsule.
The rate at which the beneficial agent is discharged from the delivery device is determined by many factors including the type of osmotic agent, the permeability of the semipermeable membrane walls, and the size and shape of the exit passage. One manner in which the delivery rate of the beneficial agent is controlled is by a flow moderator in the exit passage of the capsule which generally consist of a tubular passage having a particular cross sectional area and length.
In the known osmotic delivery systems, an osmotic tablet such as salt is placed inside the capsule and a membrane plug is placed in an open end of the capsule to provide a semipermeable wall. The membrane plug seals the interior of the capsule from the exterior environment permitting only certain liquid molecules from the environment to permeate through the membrane plug into the interior of the capsule. The membrane plug is impermeable to items within the capsule including the osmotic agent and the beneficial agent. The rate at which liquid permeates the membrane plug and enters the capsule varies depending upon the type of membrane material and the size and shape of the membrane plug. The rate at which the liquid passes through the membrane plug controls the rate at which the osmotic agent expands driving the beneficial agent from the delivery system through the exit passage. Accordingly, the rate of delivery of the beneficial agent from the osmotic delivery system is controllable by varying the permeability coefficient of the membrane plug or the size of the membrane plug.
Osmotic delivery systems requiring a high beneficial agent delivery rate typically use membrane plugs having high permeability coefficients while systems requiring low beneficial agent delivery rate use membrane plugs having a low permeability coefficient. Thus, the delivery rate of the beneficial agent in a known osmotic delivery system may be varied by forming a membrane plug having the same size and shape from different semipermeable materials. The use of a different membrane material for each system in which a different beneficial agent delivery rate is desired requires the development and manufacture of many different membrane materials and the manufacture of many different membrane plugs.
Some types of membrane plugs can swell and expand significantly when wetted. This ability to swell provides a self-sealing function between the membrane plug and the capsule walls and prevents the need for an adhesive to retain the membrane plug inside the capsule. When the membrane plug is inserted in an open end of a rigid capsule, the space for the membrane plug to swell and expand is limited by the capsule walls, thus, the membrane plug will sometimes be performing in a constrained condition. This constraint of the membrane plug causes a change in the membrane performance over time. For example, as the membrane plug becomes constrained due to swelling the morphology of the membrane material changes resulting from cold creep. This causes the beneficial agent delivery rate to change over time.
Due to the above-identified problem associated with the current osmotic delivery systems, it is costly and particularly difficult to administer beneficial agents from an osmotic delivery system at different desired delivery rates with the same system. A different membrane plug material must be selected for each application depending on the beneficial agent delivery rate desired.